Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis

Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient´s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients.European Research Council (ERC) European Commission 340918official Spanish institutions for funding scientific biomedical researchCIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN)Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigacio' n para la Salud (FIS) - European Regional Development Fund PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206 PI14/01919 PI14/00853 PI14/01374 PI14/00972 PI14/00728The Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigacio' n para la Salud (FIS) - European Regional Development Fund PI14/01471 PI16/00473 PI16/00662 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441 PI17/00508Especial Action Project "Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus"La Caixa Foundation 2013ACUP00194ICREA under the ICREA Academia programSEMERGEN grantDepartment of Health of the Government of Navarra 61/ 2015FundacioLa Maratode TV 201630.10AstraZenecaJunta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018Center for Forestry Research & Experimentation (CIEF)European Commission PROMETEO/ 2017/017Balearic Islands Government 35/2011European Commission PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576 PI19/00017 PI19/01226 PI19/00781 PI19/01560 PI19/01332 PI20/01802 PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/0115

Impact of a Gender-Neutral HPV Vaccination Program in Men Who Have Sex with Men (MSM)

[EN] A major challenge in human papillomavirus (HPV) vaccine programs is the universal gender-neutral recommendation, as well as estimation of its long-term effect. The objective of this study is to predict the added benefit of male vaccination, especially in men who have sex with men (MSM), and to analyze the impact of the program on society. We propose a mathematical model of the HPV infection based on a network paradigm. Data from Spain allowed constructing the sexual network. HPV force of infection was taken from literature. Different scenarios using variable vaccine coverage in both males and females were studied. Strong herd immunity is shown in the heterosexual population, with an important decrease of HPV 6/11 infections both in men and in unvaccinated women with an only-women vaccination at 14 years of age. No impact of this program occurred in the infection incidence in MSM. This group would only benefit from a vaccination program that includes males. However, the impact at short term would be lower than in heterosexual men. The protection of MSM can only be achieved by direct vaccination of males. This may have important consequences for public health.This paper has been supported by the Spanish Ministerio de Economía, Industria y Competitividad (MINECO), the Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER UE) grant MTM2017-89664-P. This paper has been supported by the European Union through the Operational Program of the [European Regional Development Fund (ERDF)/European Social Fund (ESF)] of the Valencian Community 2014¿2020. Files: GJIDI/2018/A/010 and GJIDI/2018/A/009Diez-Domingo, J.; Sánchez-Alonso, V.; Villanueva Micó, RJ.; Acedo, L.; Tuells, J. (2021). Impact of a Gender-Neutral HPV Vaccination Program in Men Who Have Sex with Men (MSM). International Journal of Environmental research and Public Health (Online). 18(3):1-11. https://doi.org/10.3390/ijerph18030963S11118

On the Elimination of Infections Related to Oncogenic Human Papillomavirus: an Approach using a Computational Network Model

[EN] Cervical cancer is the fourth most common malignancy in women worldwide, although it is preventable with prophylactic HPV vaccination. HPV transmission-dynamic models can predict the potential for the global elimination of cervical cancer. The random network model is a new approach that allows individuals to be followed, and to implement a given vaccination policy according to their clinical records. We developed an HPV transmission-dynamic model on a lifetime sexual partners network based on individual contacts, also accounting for the sexual behavior of men who have sex with men (MSM). We analyzed the decline in the prevalence of HPV infection in a scenario of 75% and 90% coverage for both sexes. An important herd immunity effect for men and women was observed in the heterosexual network, even with 75% coverage. However, HPV infections are persistent in the MSM population, with sustained circulation of the virus among unvaccinated individuals. Coverage around 75% of both sexes would be necessary to eliminate HPV-related conditions in women within five decades. Nevertheless, the variation in the decline in infection in the long term between a vaccination coverage of 75% and 90% is relatively small, suggesting that reaching coverage of around 70-75% in the heterosexual network may be enough to confer high protection. Nevertheless, HPV elimination may be achieved if men's coverage is strictly controlled. This accurate representation of HPV transmission demonstrates the need to maintain high HPV vaccination coverage, especially in men, for whom the cost-effectiveness of vaccination is questioned.This work has been supported by the Spanish Ministerio de Economia, Industria y Competitividad (MINECO), the Agencia Estatal de Investigacion (AEI) and Fondo Europeo de Desarrollo Regional (FEDER UE), grant MTM2017-89664-P. Authors also wish to acknowledge Maria Giovanna Ferrario, Victor Latorre, and the Medical Statistics Consulting team (Valencia, Spain) for their collaboration in writing this manuscript.Muñoz-Quiles, C.; Diez-Domingo, J.; Acedo, L.; Sánchez-Alonso, V.; Villanueva Micó, RJ. (2021). On the Elimination of Infections Related to Oncogenic Human Papillomavirus: an Approach using a Computational Network Model. Viruses. 13(5):1-12. https://doi.org/10.3390/v13050906S11213

Calibrating a large network model describing the transmission dynamics of the human papillomavirus (HPV) using a Particle Swarm Optimization (PSO) algorithm in a distributed computing environment

[EN] Working in large networks applied to epidemiological-type models has led us to design a simple but e↵ective computed distributed environment to perform a large amount of model simulations in a reasonable time in order to study the behavior of these models and to calibrate them. Finding the model parameters that best fit the available data in the designed distributed computing environment becomes a challenge and it is necessary to implement reliable algorithms for model calibration. In this paper, we have adapted the random PSO algorithm to our distributed computing environment to be applied to the calibration of a Papillomavirus transmission dynamics model on a lifetime sexual partners network. And we have obtained a good fitting saving time and calculations compared with the exhaustive searching strategy we have been using so far.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work has been partially supported by the Ministerio de Economa y Competitividad Grants MTM2013-41765-P and TIN 2014-54806-R.Acedo Rodríguez, L.; Burgos-Simon, C.; Hidalgo, J.; Sánchez-Alonso, V.; Villanueva Micó, RJ.; Villanueva-Oller, J. (2018). Calibrating a large network model describing the transmission dynamics of the human papillomavirus (HPV) using a Particle Swarm Optimization (PSO) algorithm in a distributed computing environment. International Journal of High Performance Computing Applications. 32(5):721-728. https://doi.org/10.1177/1094342017697862S721728325Acedo, L., Lamprianidou, E., Moraño, J.-A., Villanueva-Oller, J., & Villanueva, R.-J. (2015). Firing patterns in a random network cellular automata model of the brain. Physica A: Statistical Mechanics and its Applications, 435, 111-119. doi:10.1016/j.physa.2015.05.017Acedo, L., Moraño, J.-A., Villanueva, R.-J., Villanueva-Oller, J., & Díez-Domingo, J. (2011). Using random networks to study the dynamics of respiratory syncytial virus (RSV) in the Spanish region of Valencia. Mathematical and Computer Modelling, 54(7-8), 1650-1654. doi:10.1016/j.mcm.2010.11.068Castellsagué, X., Iftner, T., Roura, E., Vidart, J. A., Kjaer, S. K., … Bosch, F. X. (2012). Prevalence and genotype distribution of human papillomavirus infection of the cervix in Spain: The CLEOPATRE study. Journal of Medical Virology, 84(6), 947-956. doi:10.1002/jmv.23282Cortés, J.-C., Colmenar, J.-M., Hidalgo, J.-I., Sánchez-Sánchez, A., Santonja, F.-J., & Villanueva, R.-J. (2016). Modeling and predicting the Spanish Bachillerato academic results over the next few years using a random network model. Physica A: Statistical Mechanics and its Applications, 442, 36-49. doi:10.1016/j.physa.2015.08.032Elbasha, E. H., Dasbach, E. J., & Insinga, R. P. (2007). Model for Assessing Human Papillomavirus Vaccination Strategies. Emerging Infectious Diseases, 13(1), 28-41. doi:10.3201/eid1301.060438González-Parra, G., Villanueva, R.-J., Ruiz-Baragaño, J., & Moraño, J.-A. (2015). Modelling influenza A(H1N1) 2009 epidemics using a random network in a distributed computing environment. Acta Tropica, 143, 29-35. doi:10.1016/j.actatropica.2014.12.008Khemka, N., & Jacob, C. (2010). Exploratory Toolkit for Evolutionary and Swarm-Based Optimization. The Mathematica Journal, 11(3), 376-391. doi:10.3888/tmj.11.3-

Nutrición e Inflamación: mediadores epigenéticos

III Congreso de Alimentación, Nutrición y Dietética. Combinar la nutrición comunitaria y personalizada: nuevos retos

Paradigmatic de novo GRIN1 variants recapitulate pathophysiological mechanisms underlying GRIN1-related disorder clinical spectrum

Background: GRIN-related disorders (GRD), the so-called grinpathies, is a group of rare encephalopathies caused by mutations affecting GRIN genes (mostly GRIN1, GRIN2A and GRIN2B genes), which encode for the GluN subunit of the N-methyl D-aspartate (NMDA) type ionotropic glutamate receptors. A growing number of functional studies indicate that GRIN-encoded GluN1 subunit disturbances can be dichotomically classified into gain- and loss-of-function, although intermediate complex scenarios are often present. Methods: In this study, we aimed to delineate the structural and functional alterations of GRIN1 disease-associated variants, and their correlations with clinical symptoms in a Spanish cohort of 15 paediatric encephalopathy patients harbouring these variants. Results: Patients harbouring GRIN1 disease-associated variants have been clinically deeplyphenotyped. Further, using computational and in vitro approaches, we identified different critical checkpoints affecting GluN1 biogenesis (protein stability, subunit assembly and surface trafficking) and/or NMDAR biophysical properties, and their association with GRD clinical symptoms. Conclusions: Our findings show a strong correlation between GRIN1 variants-associated structural and functional outcomes. This structural-functional stratification provides relevant insights of genotypephenotype association, contributing to future precision medicine of GRIN1-related encephalo

Association Patterns in Saproxylic Insect Networks in Three Iberian Mediterranean Woodlands and Their Resistance to Microhabitat Loss

The assessment of the relationship between species diversity, species interactions and environmental characteristics is indispensable for understanding network architecture and ecological distribution in complex networks. Saproxylic insect communities inhabiting tree hollow microhabitats within Mediterranean woodlands are highly dependent on woodland configuration and on microhabitat supply they harbor, so can be studied under the network analysis perspective. We assessed the differences in interacting patterns according to woodland site, and analysed the importance of functional species in modelling network architecture. We then evaluated their implications for saproxylic assemblages’ persistence, through simulations of three possible scenarios of loss of tree hollow microhabitat. Tree hollow-saproxylic insect networks per woodland site presented a significant nested pattern. Those woodlands with higher complexity of tree individuals and tree hollow microhabitats also housed higher species/interactions diversity and complexity of saproxylic networks, and exhibited a higher degree of nestedness, suggesting that a higher woodland complexity positively influences saproxylic diversity and interaction complexity, thus determining higher degree of nestedness. Moreover, the number of insects acting as key interconnectors (nodes falling into the core region, using core/periphery tests) was similar among woodland sites, but the species identity varied on each. Such differences in insect core composition among woodland sites suggest the functional role they depict at woodland scale. Tree hollows acting as core corresponded with large tree hollows near the ground and simultaneously housing various breeding microsites, whereas core insects were species mediating relevant ecological interactions within saproxylic communities, e.g. predation, competitive or facilitation interactions. Differences in network patterns and tree hollow characteristics among woodland sites clearly defined different sensitivity to microhabitat loss, and higher saproxylic diversity and woodland complexity showed positive relation with robustness. These results highlight that woodland complexity goes hand in hand with biotic and ecological complexity of saproxylic networks, and together exhibited positive effects on network robustness.The research Projects I+D CGL2011-23658 y CGL2012-31669 of the Spanish Minister of Science provided economic support

Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis

Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient ' s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients